COVID-19-associated Coagulopathy Characterization using Rotational Thromboelastometry in a Prospective, Observational Cohort Study: The HemoCoV Study

Authors

  • Anabela Rodrigues Transfusion Medicine Department. Hospital Santa Maria. Centro Hospitalar Universitário Lisboa Norte. Lisbon.
  • Tiago Dias Domingues Centro de Estatística e Aplicações – CEAUL. Faculdade de Ciências. Universidade de Lisboa. Lisbon. https://orcid.org/0000-0002-4034-4276
  • Gustavo Nobre Jesus Intensive Medicine Department. Clínica Universitária de Medicina Intensiva. Hospital Santa Maria. Centro Hospitalar Universitário Lisboa Norte. Lisbon; Clínica Universitária de Medicina Intensiva. Faculdade de Medicina. Universidade de Lisboa. Lisbon. https://orcid.org/0000-0003-1042-3392
  • Ana Garção Transfusion Medicine Department. Hospital Santa Maria. Centro Hospitalar Universitário Lisboa Norte. Lisbon. https://orcid.org/0000-0002-1170-7808
  • Ana Rita Rodrigues Intensive Medicine Department. Clínica Universitária de Medicina Intensiva. Hospital Santa Maria. Centro Hospitalar Universitário Lisboa Norte. Lisbon. https://orcid.org/0000-0003-0726-0123
  • Catarina Jacinto Correia Transfusion Medicine Department. Hospital Santa Maria. Centro Hospitalar Universitário Lisboa Norte. Lisbon. https://orcid.org/0000-0002-7533-545X
  • Carla Leal Pereira Transfusion Medicine Department. Hospital Santa Maria. Centro Hospitalar Universitário Lisboa Norte. Lisbon. https://orcid.org/0000-0002-1947-819X
  • Dulce Correia Intensive Medicine Department. Clínica Universitária de Medicina Intensiva. Hospital Santa Maria. Centro Hospitalar Universitário Lisboa Norte. Lisbon. https://orcid.org/0000-0002-6275-8699
  • Álvaro Beleza Transfusion Medicine Department. Hospital Santa Maria. Centro Hospitalar Universitário Lisboa Norte. Lisbon. https://orcid.org/0000-0001-7123-6991
  • João Miguel Ribeiro Intensive Medicine Department. Clínica Universitária de Medicina Intensiva. Hospital Santa Maria. Centro Hospitalar Universitário Lisboa Norte. Lisbon. https://orcid.org/0000-0001-7207-8948

DOI:

https://doi.org/10.20344/amp.19475

Keywords:

Blood Coagulation Disorders, COVID-19, Fibrinolysis, Thromboelastometry, Thrombosis

Abstract

Introduction: COVID-19-associated coagulopathy includes systemic and endothelial inflammation with coagulation dysregulation related to immunothrombosis. The aim of this study was to characterize this complication of SARS-CoV-2 infection in patients with moderate to severe COVID-19.
Methods: An open-label, prospective observational study conducted in patients with COVID-19 moderate to severe acute respiratory failure admitted to an intensive care unit (ICU). Coagulation testing, including thromboelastometry, biochemical analysis and clinical variables, were collected at prespecified time points during the 30 days of ICU stay.
Results: The study included 145 patients, 73.8% male, with a median age of 68 years (interquartile range - IQR 55 - 74). The most prevalent comorbidities were arterial hypertension (63.4%), obesity (44.1%) and diabetes (22.1%). Simplified acute physiology score II (SAPS II) was on average 43.5 (11 - 105) and sequential organ failure assessment (SOFA) at admission was 7.5 (0 - 14). During ICU stay, 66.9% of patients underwent invasive mechanical ventilation and 18.4% extracorporeal membrane oxygenation support; thrombotic and hemorrhagic events occurred in 22.1% and 15.1% of the patients respectively; anticoagulation with heparin was present in 99.2% of patients since early ICU stay. Death occurred in 35% of patients. Longitudinal studies revealed changes in almost all coagulation tests during the ICU stay. SOFA score, lymphocyte counts, some biochemical, inflammatory and coagulation parameters, including hypercoagulability and hypofibrinolysis seen in thromboelastometry, differed significantly (p < 0.05), between ICU admission and discharge. Hypercoagulability and hypofibrinolysis persisted throughout ICU hospitalization, showing higher incidence and severity in non-survivors.
Conclusion: COVID-19-associated coagulopathy is characterized by hypercoagulability and hypofibrinolysis from ICU admission, and persisted throughout the clinical course in severe COVID-19. These changes were more pronounced in patients with higher disease burden and in non-survivors.

Downloads

Download data is not yet available.

References

Connors JA, Iba T, Gandhi RT. Thrombosis and COVID-19: controversies and (tentative) conclusions. Clin Infect Dis. 2021;73:2294-7.

Magnani HN. Rational for the role of heparin and related gag antithrombotics in COVID-19 infection. Clin Appl Thromb Hemost. 2021;27:1-26.

Thachil J, Juffermans NP, Ranucci M, Connors JM, Warkentin TE, Ortel TL, et al. ISTH DIC subcommittee communication on anticoagulation in COVID-19. J Thromb Haemost. 2020;18:2138-44.

Ramacciotti E, Macedo AS, Biagioni RB, Caffaro RA, Lopes RD, Guerra JC, et al. Evidence-based guidance for the antithrombotic management in patients with coronavirus disease (COVID-19) in 2020. Clin Appl Thromb Hemost. 2020;26:1-8.

Flaczyk A, Rosovsky RP, Reed CT, Bankhead-Kebdall BK, Bittner E, Chang MG. Comparison of published Guidelines for Management of Coagulopathy and Thrombosis in Critically Ill Patients with COVID-19: implications for clinical practice and future investigations. Critical Care. 2020;24:559.

Bikdeli B, Madhavan MV, Jimenez D, Chuich T, Dreyfust I, Driggin E, et al. COVID-19 and thrombotic or thromboembolic disease: implications for prevention, antithrombotic therapy, and follow-up. JACC state-of-theart-review. J Am Coll Cardiol. 2020;75:2950-73.

Riva G, Nasillo V, Tagliafico E, Trenti T, Comoli P, Luppi M. COVID-19: more than a cytokine strom. Critical Care. 2020;24:549-51.

Zanza C, Racca F, Longhitano Y, Piccioni A, Franceschi F, Artico M, et al. Risk management and treatment of coagulation disorders related to COVID-19 infection. Int J Environ Res Public Health. 2021;18:1268.

Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020;18:844-7.

Han H, Yang L, Liu R, Liu F, Wu KL, Li J, et al. Prominent changes in blood coagulation of patients with SARS-CoV-2 infection. Clin Chem Lab Med. 2020;58:1116-20.

Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395:1054-62.

Wu C, Chen X, Cai Y, Xia J, Zhou X, Xu S, et al. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Intern Med. 2020;180:934-43.

Gao Y, Li T, Han M, Li X, Wu D, Xu Y, et al. diagnostic utility of clinical laboratory data determinations for patients with the severe COVID-19. J Med Virol. 2020;92:791-6.

Hu B, Huang S, Yin L. The cytokine storm and COVID-19. J Med Virol. 2021;93:250-6.

Zanza C, RomensKaya T, Manetti C, Franceschi F, La Russa R, Bertozzi G, et al. Cytokine storm in COVID-19 immunopathogenesis and therapy. Medicina. 2022;58:144.

Schulman S, Sholzberg M, Spyropoulos AC, Zarychanski R, Resnick HE, Bradbury CA, et al, on behalf of the International Society on Thrombosis and Haemostasis. ISTH guidelines for antithrombotic treatment in COVID-19. J Thromb Haemost. 2022;20:2214-25.

COVID-19 Treatment Guidelines Panel. Coronavirus disease 2019 (COVID-19) treatment guidelines. National Institutes of Health (NIH). [cited 2023 Mar 11]. Available at: https://www.covid19treatmentguidelines.nih.gov.

Cuker A, Tseng EK, Nieuwlaat R, Angchaisuksiri P, Blair C, Dane K, et al. American Society of Hematology 2021 Guidelines on the use of anticoagulation for thromboprophylaxis in patients with COVID-19. Blood Advances. 2021;5:872-88.

Cuker A, Tseng EK, Nieuwlaat R, Angchaisuksiri P, Blair C, Dane K, et al. American Society of Hematology living Guidelines on the use of anticoagulation for thromboprophylaxis in patients with COVID-19: january 22 update on the use of therapeutic-intensity anticoagulation in acutely ill patients. Blood Advances. 2022;6:4915-23.

Kreuziger LB, Sholzberg M, Cushman M. Anticoagulation in hospitalized patients with COVID-19. Blood. 2022;140:809-14.

Barnes GD, Burnett A, Allen A, Ansell J, Blumenstein M, Clark NP, et al. Thromboembolic prevention and anticoagulation therapy during the COVID-19 pandemic: update clinical guidelines from the anticoagulation forum. J Thromb Thrombolysis. 2022;54:197-210.

Von Elm E, Altman DG, Egger M, Pocok SJ, Gotzsche PC, Vandenbroucke JP, for the STROBE Initiative. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. PLOS Med. 2007;4:e296.

Marshall JC, Murthy S, Diaz SJ and collaborators of WHO Working Group on the Clinical Characterization and Management of COVID-19 infection. A minimal common outcome measure set for COVID-19 clinical research. WHO Working Group on the Clinical Characterization and Management of COVID-19 infection. Lancet Infect Dis. 2020;20:e192-7.

Estcourt L, Birchall J, Allard S, Bassey SJ, Hersey P, Kerr JP, et al, on behalf of British Committee for Standards in Haematology. Guidelines for the use of platelet transfusions. Br J Haematol. 2017;176:365-94.

U.S. Department of Health and Human Services. Common Terminology Criteria for Adverse Events (CTCAE) v5.0. 2017. [cited 2017 Nov 27]. Available from: https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/CTCAE_v5_Quick_Reference_8.5x11.pdf.

Schwartz GJ, Furth SL. Glomerular filtration rate measurement and estimation in chronic kidney disease. Pediatr Nephrol. 2007;22:1839-48.

O’Callaghan CA, Shine B, Lasserson DS. Chronic kidney disease: a large-scale population-based study of the effects of introducing the CKD-EPI formula for eGFR reporting. BMJ Open. 2011;1:e000308.

Gorlinger K, Pérez-Ferrer A, Dirkmann D, Saner F, Maegele M, Calatayud AA, et al. The role of evidence-based algorithms for rotational thromboelastometry-guided bleeding management. Korean J Anesthesiol. 2019;72:297-322.

Gorlinger K, Pérez-Ferrer A. Algoritmo basado en test POC para el manejo de la hemorragia aguda. In: Pérez-Ferrer A, Garcia-Erce JA, editors. Medicina transfusional. Patient blood management. 2nd ed. Madrid: Editorial Medica Panamericana; 2019. p.75-110.

International Society on Thrombosis and Haemostasis. Sepsis-induced coagulopathy [SIC] algorithm. A practical guide to haemostasis. [cited 2022 Sep 27]. Available from: https://practical-haemostasis.com/Clinical%20Prediction%20Scores/Formulae%20code%20and%20formulae/Formulae/DIC/isth_sic_score.html.

International Society of Blood Transfusion. Criteria for disseminated intravascular coagulation [DIC]. [cited 2023 Mar 11]. Available from: https://www.mdcalc.com/isth-criteria-disseminated-intravascularcoagulation-dic.

Mc Michael AB, Ryerson LM, Ratano D, Fan E, Faraoni D, Annich GM. 2021 ELSO Adult and pediatric anticoagulation guidelines. ASAIO J. 2022;68:303-10.

Almskog LM, Wikman A, Svensson J, Wanecek M, Bottaí M, van der Linden J, et al. Rotational thromboelastometry results are associated with care level in COVID-19. J Thromb Thrombolysis. 2021;51:437-45.

Gonenli MG, Komesti Z, Incir S, Yalçin O, Akay OM. Rotational thromboelastometry reveals distinct coagulation profiles for patients with COVID-19 depending on disease severity. Clin App Thromb Hemost. 2021;27:1-7.

Aires RB, Soares AS, Gomides AP, Nicola AM, Teixeira-Carvalho A, Silva DL, et al. Thromboelastometry demonstrates endogenous coagulation activation in nonsevere and severe COVID-19 patients and has applicability as a decision algorithm for intervention. PLoS One. 2022;14;17:e0262600.

Rodrigues A, Seara Sevivas T, Leal Pereira C, Caiado A, Robalo Nunes A. Viscoelastic tests in the evaluation of haemostatic disorders in SARSCoV-2 infection. Acta Med Port. 2020;33:1-13.

Spieza L, Boscolo A, Poletto F, Cerruti L, Tiberio I, Campeloo E, et al. COVID-19-related severe hypercoagulability in patients admitted to intensive care unit for acute respiratory failure. Thromb Haemost. 2020;120:998-1000.

Wright FL, Vogler TO, Moore EE, Moore MB, Wohlauer MV, Urbans S, et al. Fibrinolysis shutdown. Correlation with thromboembolic events in severe COVID-19 infection. J Am Coll Surg. 2020;231:193-203e1.

Heinz C, Miesbach W, Hermann E, Sonnatagbauer M, Raimann FJ, Zacharowski K, et al. Greater fibrinolysis resistance but no greater platelet aggregation in critically ill COVID-19 patients. Anesthesiol. 2021;134:457-67.

Creel-Bulos C, Auld SC, Caridi-Scheible M, Barker NA, Friend S, Gaddh M, et al. Fibrinolysis shutdown and thrombosis in a COVID-19 ICU. Shock. 2021;55:316-20.

Zhan H, Chen H, Liu C, Cheng L, Yan S, Li H, et al. Diagnostic value of D-dimer in COVID-19. A meta-analysis and meta-regression. Clin App Thromb Hemost. 2021;27:1-10.

Jaim S, Subhashimi H, Kumari G, Narayan A, Kumar A, Ranjan P, et al. Fibrinogen in COVID-19: interpreting from current evidence. JAM. 2020;9:5-10.

Zou Y, Guo H, Zhang Y, Zhang Z, Liu Y, Wang J, et al. Analysis of coagulation parameters in patients with COVID-19 in Shangai, China. Biosci Trends. 2020;14:285-9.

Henry BM, de Oliveira MH, Benoit S, Plebani M, Lippi G. Hematologic, biochemical and immune biomarker abnormalities associated with severe illness and mortality in coronavirus disease 2019 (COVID-19): a meta-analysis. Clin Chem Lab Med. 2020;58:1021-8.

Published

2023-07-03

How to Cite

1.
Rodrigues A, Dias Domingues T, Nobre Jesus G, Garção A, Rodrigues AR, Jacinto Correia C, Leal Pereira C, Correia D, Beleza Álvaro, Ribeiro JM. COVID-19-associated Coagulopathy Characterization using Rotational Thromboelastometry in a Prospective, Observational Cohort Study: The HemoCoV Study. Acta Med Port [Internet]. 2023 Jul. 3 [cited 2024 Apr. 25];36(7-8):496-505. Available from: https://www.actamedicaportuguesa.com/revista/index.php/amp/article/view/19475